Recognizing that cartilage degradation is an expected consequence of inflammatory and degenerative joint disease and that the proteoglycans, collagen and chondrocytes comprising cartilage are antigenic, studies are examining the potential immunopathologic significance of sensitization to such constituents as relates to the causation and/or perpetuation of joint inflammation and cartilage destruction in both human and experimental models of joint disease. Studies have identified proteoglycans within synovial fluid and the lysophagosomes of its cell content, have shown humoral and cell mediated immune responses to such determinants in patients having diverse articular diseases and have demonstrated the capacity of proteoglycans to modulate T-cell function. In addition, the immunopathologic significance of cell mediated immunity in the pathogenesis of articular cartilage destruction is being evaluated. It has been shown that lymphokines, induced by mitogen, proteoglycan and collagen antigenic stimulation, may through monocyte interaction, directly degrade the proteoglycan matrix of cartilage as well as, in a reversible manner, suppress chondrocyte glycosaminoglycan synthesis. In addition, lymphokines have been shown capable of modulating lysosomal hydrolase induced destruction of cartilage proteoglycans.